Host responses to therapy and the tumour microenvironment contribute to the development of tumour resistance

Researcher

Project Details

In almost all metastatic cancer treatments including colorectal cancer (CRC) a small fraction of tumour cells survive invariably giving rise to recurrence. Thus highlights the need to understand the mechanisms of tumour resistance to treatment.

Antitumor therapies, in addition to direct cytotoxic effects on tumour cells, also provoke a host response which plays a role in therapy resistance. We have shown drug treatments induce tumour promoting host responses even in the absence of tumour. In addition, tumours surviving cytotoxic treatments undergo a rapid but transient change known as epithelial to mesenchymal transition (EMT).We hypothesize that EMT bestows surviving tumour cells with transient drug resistance. In the clinic tumours are responsive to several rounds of drug treatment before permanent resistance develops. Interestingly we found tumours survive and undergo EMT only when they reside in close proximity to host immune cells known to secrete tumour protective factors. The results suggest a significant role for the immune system and the tumour microenvironment in the development of tumour resistance.

We are investigating the tumour microenvironment and the host response contributions to resistance development, with specific emphasis on the contribution of immune cells including macrophages/neutrophils and their secreted molecules.